Stanislav Tabakaev

Peritoneal carcinomatosis is one of the most challenging problems in modern oncology, due to its unfavorable progression pattern for malignant tumors in various locations. It is also a relatively rare occurrence in the progression of cervical cancer and is more common in tumors in other locations. The prognostic significance of peritoneal involvement in cervical cancer remains unclear. The impact of neoadjuvant chemotherapy on the peritoneal area and tumor spread also remains poorly understood. According to various authors, peritoneal carcinomatosis occurs in 1–6 % of patients with malignant cervical tumors. In this case report, we presented a rare case of peritoneal carcinomatosis associated with recurrent cervical cancer.

Background . Luminal breast cancer, comprising 60–80 % of cases, is characterized by a high frequency of bone metastasis, necessitating continuous surveillance for early detection of distant metastases. Traditional imaging methods have limited sensitivity, especially for small lesions. Therefore, the development of highly sensitive methods for early diagnosis is relevant. Targeted radionuclide imaging of the gastrin-releasing peptide receptor (GRPR) using antagonist-based radiopharmaceuticals, such as [ ^99ᵐ Tc]Tc-DB8 is a promising non-invasive method for detecting small lesions. The aim of the study was to demonstrate the potential of [ ^99ᵐ Tc]Tc-DB8 for detecting bone metastases in patients with luminal breast cancer. Case report 1 . A 51- year-old woman diagnosed with stage IIIC right breast cancer (T2N3M0), with multicentric growth, metastatic involvement of the axillary and subclavian lymph nodes, underwent SPECT/CT 2 hours after the intravenous administration of [ ^99ᵐ Tc]Tc-DB8 at a protein dose of 80 μg. The detection of a high-uptake [ ^99ᵐ Tc]Tc-DB8 lesion in the right 5th rib, confrmed as a lytic bone destruction on CT, indicated a high suspicion of bone metastasis. Followup chest CT showed an area of uneven sclerotic changes, interpreted as a response to therapy. Case report 2 . A 42-year-old woman was diagnosed with stage IV right breast cancer (T1N1M1), metastatic involvement of the axillary lymph node, and multiple bone metastases. A SPECT/CT performed 2 hours after the intravenous injection of [ ^99ᵐ Tc]Tc-DB8 at a dose of 80 μg revealed high uptake of the radiopharmaceutical in the primary tumor, metastatic lymph nodes, and extensive bone metastases. Specifcally, the radiopharmaceutical accumulated in the L2-S2 vertebrae, the right ilium and ischium, and the posterior segment of the 7th rib on the right, identifying these as metastatic sites. Conclusion . Results of the clinical study on [ ^99ᵐ Tc]Tc-DB8 demonstrated its high effcacy in detecting bone metastases in patients with luminal breast cancer.

Introduction : Solitary fibrous tumor (SFT) — a rare mesenchymal tumor of fibroblastic origin. Solitary fibrous tumor is not a tumor of the pleura itself, unlike diffuse mesothelioma. The SFT was first described by E. Wagner in 1870. Non-specific clinical manifestations of solitary fibrous tumor complicate the diagnostic search and significantly expand the differential diagnostic range. Purpose : To demonstrate a rare case of solitary fibrous tumor of the pleura and to show, using a clinical case as an example, the difficulties of its diagnosis. Materials and methods : Multislice computed tomography (MSCT) of the chest organs performed to the patient with complaints of cough and shortness of breath during intense physical activity. Formation was detected with clear contours, a heterogeneous structure, located subpleurally was revealed. Results : The presented observation demonstrates non-specific radiological manifestations of a solitary fibrous tumor and illustrates the importance of correct interpretation of data and choice of diagnostic algorithm.

Introduction. Giant cell tumor (GCT) of bone is a relatively rare neoplasm. Its malignant transformation in the form of sarcomatous changes occurs in 8–10 % of cases. The literature lacks data on radiological signs and differential diagnostic criteria of primary malignant GCT of bone. Clear guidelines on the density range of the affected area for differential diagnosis are also absent. Aim. To analyze dynamics of tumor density changes in patients with malignant GCT of bone using computed tomography densitometry. Materials and methods. Ten patients (mean age 45.8 ± 4.2 years, range 28–58 years) with malignant GCT of bone were examined. All underwent treatment with denosumab with subsequent surgical intervention. Bone changes were assessed visually. Densitometric analysis was performed in accordance with a method developed by us involving determination of tumor density in Housefield units (HU) and relative tumor density index (k) (ratio between tumor density and density of the unaffected limb at the same level). Results. After 6 injections of denosumab, a clear sclerotic rim appeared at the tumor periphery containing thin lines of ossification. Analysis of densitometric parameters showed that tumor density after denosumab administration increased from 46.3 (median (Мe) 35.0; interquartile range (IQR) 51.4) HU to 88.8 (Мe 84.8; IQR 118.4) HU, while relative tumor density index increased from 0.33 (Me 0.22; IQR 0.45) to 0.68 (Me 0.62; IQR 0.89). Earlier we have published threshold values of these parameters (≥139.5 HU and ≥0.97, respectively) at which probability of residual tumor is lowered (sensitivity 81.8 %, specificity 96.6 %). Taking into account these values, 9 of 10 patients required continuation of therapy. Conclusion. Computed tomography densitometry allows to evaluate changes caused by denosumab therapy in patients with malignant GCT of bone. According to radiological data, progression of this disease has unique features. Taking into account histological types of malignant GCT, longer periods of observation and denosumab administration or changes in treatment tactics at the preoperative stage can be considered, as well as potential use of this drug in other primary bone tumors.

Introduction. Bone tumors are heterogeneous group of skeletal neoplasms characterized by frequent recurrences, aggressive clinical course and low survival rates. The development of new treatment methods continues to pose pressing challenges. Radical intraoperative thermal ablation (RIT) using high-temperature exposure is emerging as a new and promising strategy for organ-preserving treatment. This study focuses on the effect of thermal ablation (TA) on tumors.Objective of the Study to assess the impact of TA (using the RIT method) on the viability of tumor cells.Material and Methods. The study included 8 patients with bone tumors. Tumors underwent TA at a temperature of 60 °C for 30 minutes ex vivo. Apoptosis was studied in tumor tissue samples before and after TA. Apoptosis was assessed using two methods: flow cytometry and the TUNEL assay.Results. The TA procedure developed by our scientific group represents a promising organ-preserving approach for treating malignant bone tumors. A temperature regime of 60 °C for 30 minutes was effective in initiating tumor cells death. This was confirmed by two independent methods – flow cytometry and TUNEL assay – which demonstrated a significant increase in the number of apoptotic cells immediately following the procedure and a notable rise in the number of cells exhibiting signs of late apoptosis one hour post thermal ablation. Therefore, the collected data confirm a pronounced antitumor effect immediately after implementing RIT.Conclusion. The findings confirm that RIT is a viable organ-preserving method for treating bone tumors, meriting further investigation to expand its application in clinical practice.

Circulating small extracellular vesicles (sEVs) are emerging as potential biomarkers for glioblastoma progression. This study aimed to compare the levels of matrix metalloproteinases (MMP2 and MMP9), terminal complement complex (C5b-9), and VEGF-A in circulating sEVs in glioblastoma patients (GBMPs) with and without tumor recurrence. Using differential ultracentrifugation, sEVs were isolated from blood samples of GBMPs with no tumor recurrence for over one year (n = 6) and after first relapse (n = 14). The vesicles were characterized and quantified using flow cytometry. In both groups, C5b-9 was predominantly detected on tumor-specific circulating sEVs (glial fibrillary acidic protein (GFAP)-positive sEVs) with high VEGF-A expression, while C5b-9 was significantly less frequent on sEVs with low VEGF-A expression (p < 0.05). GFAP+VEGF+dimMMP2-C5b-9+ vesicles were rarely detected in GBMPs without relapse, suggesting their potential utility as biomarkers for a favorable relapse-free prognosis. In recurrent GBMPs, a positive correlation was observed between GFAP+VEGF+bright MMP2+C5b-9+ sEVs and MGMT gene promoter methylation levels (r = 0.543, p < 0.05). Additionally, a trend toward a negative correlation was found between GFAP+VEGF+bright MMP2+C5b-9- sEVs and mutant p53 expression in primary tumor tissue (r = −0.44, p = 0.114). These findings suggest that sEV profiles may serve as valuable prognostic markers for glioblastoma recurrence and treatment responses.

Several studies have shown that the increased expression of delta–like noncanonical Notch ligand 1 (DLK-1) is associated with more aggressive tumor characteristics in patients with glioblastoma. The aim of the study was to estimate the diagnostic and prognostic values of DLK-1 serum levels in glioblastoma patients. Material and Methods. The study included 39 patients with newly diagnosed glioblastoma. The DLK-1 level was evaluated in paired serum and cerebrospinal fluid samples in glioblastoma patients before starting chemoradiotherapy (CRT). All patients with glioblastoma received combined modality treatment. The DLK-1 level in blood serum was additionally assessed during follow-up visits. Results. The median levels of DLK-1 in paired CSF and serum samples before CRT were 1.17 ng/ml (95 % CI 0.78; 2.89) and 0.27 ng/ml (95 % CI 0.26; 0.29), respectively (p=0.006). The assessment of the DLK-1 serum level in glioblastoma patients didn’t show any significant differences related to the response to therapy. In patients with tumor progression after CRT, the median serum DLK-1 level before CRT was 0.43 ng/ml, and in patients with stable disease, the median serum level was 1.7 ng/ml (p=0.012). The DLK-1 serum levels were 1.60 ng/ml and 0.32 ng/ml in patients with favorable prognosis for progression–free survival and in patients with unfavorable prognosis, respectively (p=0.005). The median concentrations of DLK-1 in serum before starting CRT were 1.01 ng/ml and 0.32 ng/ml in patients with favorable prognosis of overall survival and in patients with unfavorable prognosis, respectively (p=0.04). The DLK-1 levels in 4 weeks after CRT were 1.53 ng/ml and 0.23 ng/ml in patients with favorable prognosis of overall survival and in patients with the unfavorable prognosis, respectively (p=0.04). Conclusion. The DLK-1 serum level in patients with glioblastoma cannot be used to diagnose disease progression. However, this marker is a prognostic factor for overall and progression-free survival, and allows identification of patients with favorable and unfavorable prognosis.

Introduction. Difficult diagnosis, aggressive progression, and absence of an increase in treatment effectiveness (especially in patients with osteosarcoma and Ewing sarcoma) make malignant tumors of the bones a significant medical problem. Use of traditional therapy methods is often associated with development of drug resistance and frequent recurrences. Therefore, there is a need for new treatment strategies and overcoming of the limitations of traditional methods through their improvement, combination or substitution to achieve higher survival, lower recurrence rate, and wider availability for patients with bone tumors.Aim. To present a clinical observation of the use of a new method of radical intraoperative thermal ablation for bone tumors, assess exposure tolerance, long-term oncological and functional results.Clinical observation. This article presents a clinical case of the use of a new radical treatment method for a patient with tibial osteosarcoma who underwent intraoperative thermal ablation using a new domestic complex of local hyperthermia “Phoenix-2”.Results. A session of intraoperative thermal ablation was performed in the operating room under anesthesia directly in the wound for 48 minutes. Access to the tumor-affected bone was performed with the standard oncological approach (en-block), the bone was not transected or removed. A constant heating mode of 90 °С was used, assuming a gradual increase in temperature. Thus, 60 °С reached 20 minutes, and the temperature at the end of high-temperature exposure was 78 °С (inside the medullary canal). The operation time was 2 hours 30 minutes. The postoperative period proceeded without complications. After 38 months of follow-up, examinations did not reveal any recurrence or progression in the patient.Conclusion. The technique of radical intraoperative thermal ablation using a local hyperthermia complex Phoenix-2 is effective and allows to widen the toolkit of treatment methods for patients with bone tumors. It can serve as an alternative or addition to organ-preserving surgical treatment without costly reconstruction stages.

The purpose of the study was to develop and evaluate the technique for volumetric tumor segmentation based on diffusion-weighted magnetic resonance imaging (DW-MRI) in predicting and assessing the response to chemotherapy in patients with bladder cancer (BC). Material and Methods. We examined 26 patients with morphologically verified transitional cell carcinoma of the bladder. The group was characterized by the presence of one or several tumors with a size of 17 to 46 mm. Before planning chemotherapy according to the M-VAC scheme, a study and post-processing of DW-MRI with volumetric segmentation of lesions, assessment of the volume and apparent diffusion coefficient (ADC) in the entire tumor mass were performed. According to the ADC data, shape of the tumor and its relation to the bladder wall, the coefficient (C) for predicting the response to chemotherapy was calculated. Results. In the cases with a coefficient value below 0.51, a high risk of treatment failure was predicted, at C≥0.74, a positive effect of treatment was predicted. With a value of 0.51≤CConclusion. The method of volumetric segmentation makes it possible to predict and evaluate bladder cancer response to chemotherapy with a sufficiently high accuracy. The advantages of the method are the possibility of assessing the tumor regardless of the degree of filling of the bladder, with non-contrast MRI, and with large lesions.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ КОЛИЧЕСТВЕННЫХ ДАННЫХ КОМПЬЮТЕРНОЙ ТОМОГРАФИИ И МОРФОЛОГИЧЕСКОГО ИССЛЕДОВАНИЯ У ПАЦИЕНТОВ С ГИГАНТОКЛЕТОЧНОЙ ОПУХОЛЬЮ КОСТИ ПРИ ЛЕЧЕНИИ ДЕНОСУМАБОМ